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  1. Article ; Online: Differential effects of synthetic psychoactive cathinones and amphetamine stimulants on the gut microbiome in mice.

    Mariana Angoa-Pérez / Branislava Zagorac / Andrew D Winters / Jonathan M Greenberg / Madison Ahmad / Kevin R Theis / Donald M Kuhn

    PLoS ONE, Vol 15, Iss 1, p e

    2020  Volume 0227774

    Abstract: The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat ...

    Abstract The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat infection, diabetes, cardiovascular conditions and cancer. By comparison, drugs of abuse and addiction, which can powerfully and chronically worsen human health, have received relatively little attention in this regard. Therefore, the main objective of this study was to characterize how selected synthetic psychoactive cathinones (aka "Bath Salts") and amphetamine stimulants modify the gut microbiome. Mice were treated with mephedrone (40 mg/kg), methcathinone (80 mg/kg), methamphetamine (5 mg/kg) or 4-methyl-methamphetamine (40 mg/kg), following a binge regimen consisting of 4 injections at 2h intervals. These drugs were selected for study because they are structural analogs that contain a β-keto substituent (methcathinone), a 4-methyl group (4-methyl-methamphetamine), both substituents (mephedrone) or neither (methamphetamine). Mice were sacrificed 1, 2 or 7 days after treatment and DNA from caecum contents was subjected to 16S rRNA sequencing. We found that all drugs caused significant time- and structure-dependent alterations in the diversity and taxonomic structure of the gut microbiome. The two phyla most changed by drug treatments were Firmicutes (methcathinone, 4-methyl-methamphetamine) and Bacteriodetes (methcathinone, 4-methyl-methamphetamine, methamphetamine, mephedrone). Across time, broad microbiome changes from the phylum to genus levels were characteristic of all drugs. The present results signify that these selected psychoactive drugs, which are thought to exert their primary effects within the CNS, can have profound effects on the gut microbiome. They also suggest new avenues of investigation into the possibility that gut-derived signals could modulate drug abuse and addiction via altered communication along the gut-brain axis.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Repetitive, mild traumatic brain injury results in a progressive white matter pathology, cognitive deterioration, and a transient gut microbiota dysbiosis

    Mariana Angoa-Pérez / Branislava Zagorac / John H. Anneken / Denise I. Briggs / Andrew D. Winters / Jonathan M. Greenberg / Madison Ahmad / Kevin R. Theis / Donald M. Kuhn

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Abstract Traumatic brain injury (TBI) is often accompanied by gastrointestinal and metabolic disruptions. These systemic manifestations suggest possible involvement of the gut microbiota in head injury outcomes. Although gut dysbiosis after single, ... ...

    Abstract Abstract Traumatic brain injury (TBI) is often accompanied by gastrointestinal and metabolic disruptions. These systemic manifestations suggest possible involvement of the gut microbiota in head injury outcomes. Although gut dysbiosis after single, severe TBI has been documented, the majority of head injuries are mild, such as those that occur in athletes and military personnel exposed to repetitive head impacts. Therefore, it is important to determine if repetitive, mild TBI (rmTBI) will also disrupt the gut microbiota. Male mice were exposed to mild head impacts daily for 20 days and assessed for cognitive behavior, neuropathology and disruptions in the gut microbiota at 0, 45 or 90 days after injury. Deficits in recognition memory were evident at the late post-injury points. Brains show an early increase in microglial activation at the 0-day time point that persisted until 90 days post-injury. This was compounded by substantial increases in astrocyte reactivity and phosphorylated tau at the 90-day time point. In contrast, changes in the microbial community were minor and transient, and very few differences were observed in mice exposed to rmTBI compared to controls. While the progressive emergence of white matter damage and cognitive alterations after rmTBI resembles the alterations observed in athletes and military personnel exposed to rmTBI, these changes could not be linked to systematic modifications in the gut microbiota.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Effects of a high fat diet on gut microbiome dysbiosis in a mouse model of Gulf War Illness

    Mariana Angoa-Pérez / Branislava Zagorac / Dina M. Francescutti / Andrew D. Winters / Jonathan M. Greenberg / Madison M. Ahmad / Shannon D. Manning / Brian D. Gulbransen / Kevin R. Theis / Donald M. Kuhn

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Abstract Gulf War Illness (GWI) is a chronic health condition that appeared in Veterans after returning home from the Gulf War. The primary symptoms linked to deployment are posttraumatic stress disorder, mood disorders, GI problems and chronic fatigue. ... ...

    Abstract Abstract Gulf War Illness (GWI) is a chronic health condition that appeared in Veterans after returning home from the Gulf War. The primary symptoms linked to deployment are posttraumatic stress disorder, mood disorders, GI problems and chronic fatigue. At first glance, these symptoms are difficult to ascribe to a single pathological mechanism. However, it is now clear that each symptom can be linked individually to alterations in the gut microbiome. The primary objective of the present study was to determine if gut microbiome dysbiosis was evident in a mouse model of GWl. Because the majority of Gulf War Veterans are overweight, a second objective was to determine if a high fat diet (HF) would alter GWI outcomes. We found that the taxonomic structure of the gut microbiome was significantly altered in the GWI model and after HF exposure. Their combined effects were significantly different from either treatment alone. Most treatment-induced changes occurred at the level of phylum in Firmicutes and Bacteroidetes. If mice fed HF were returned to a normal diet, the gut microbiome recovered toward normal levels in both controls and GWI agent-treated mice. These results add support to the hypotheses that dysbiosis in the gut microbiome plays a role in GWI and that life-style risk factors such as an unhealthy diet can accentuate the effects of GWI by impacting the gut microbiome. The reversibility of the effect of HF on the gut microbiome suggests new avenues for treating GWI through dietary intervention.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Brain serotonin signaling does not determine sexual preference in male mice.

    Mariana Angoa-Pérez / Nieves Herrera-Mundo / Michael J Kane / Catherine E Sykes / John H Anneken / Dina M Francescutti / Donald M Kuhn

    PLoS ONE, Vol 10, Iss 2, p e

    2015  Volume 0118603

    Abstract: It was reported recently that male mice lacking brain serotonin (5-HT) lose their preference for females (Liu et al., 2011, Nature, 472, 95-100), suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside ...

    Abstract It was reported recently that male mice lacking brain serotonin (5-HT) lose their preference for females (Liu et al., 2011, Nature, 472, 95-100), suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2), which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female) or animate (male or female mouse in estrus) sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference.
    Keywords Medicine ; R ; Science ; Q
    Subject code 590
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors

    Michael J Kane / Mariana Angoa-Peréz / Denise I Briggs / Catherine E Sykes / Dina M Francescutti / David R Rosenberg / Donald M Kuhn

    PLoS ONE, Vol 7, Iss 11, p e

    possible relevance to autism.

    2012  Volume 48975

    Abstract: Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in ... ...

    Abstract Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circuitry. However, the manner in which these mutated genes might participate, either individually or together, to cause autism is not understood. One factor known to exert extremely broad influence on brain development and network formation, and which has been linked to autism, is the neurotransmitter serotonin. Unfortunately, very little is known about how alterations in serotonin neuronal function might contribute to autism. To test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder. Mice lacking brain serotonin (TPH2-/-) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2-/- mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism. Our findings should stimulate new studies that focus on determining how brain hyposerotonemia during critical neurodevelopmental periods can alter the maturation of synaptic circuits known to be mis-wired in autism and how prevention of such deficits might prevent this disorder.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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